Natural History of Anthrax: a Study of Primary Infected, Recovered, and Exposed Individuals (SPoRE); and Evaluation of AVA-Vaccinated Recipients

NCT ID: NCT00050310

Last Updated: 2025-12-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

200 participants

Study Classification

OBSERVATIONAL

Study Start Date

2002-10-31

Brief Summary

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This study will examine pathophysiology and immune response of anthrax in infected or exposed individuals to learn more about the disease symptoms, prevention and response to treatment. In addition, it will evaluate immune response to the anthrax vaccine AVA (Anthrax Vaccine Adsorbed) in healthy, non-infected individuals.

The following individuals may be eligible for this study:

1. People with confirmed or suspected anthrax (inhalational, cutaneous or gastrointestinal, either acute or recovering);
2. People exposed to anthrax who have no clinical symptoms.
3. Healthy people who have not been exposed to anthrax and have been vaccinated with AVA.

Those enrolled in the study will undergo the following tests and procedures.

Infected and exposed individuals:

* Symptomatic participants will have the following clinical procedures if medically necessary:
* a) blood tests for cell counts, chemistries and evidence of anthrax bacteria;
* b) nasal swab to test for evidence of anthrax
* c) chest X-ray;
* d) computed tomography (CT) scan (special X-rays to examine the lungs or abdomen);
* e) echocardiogram to examine the heart
* f) magnetic resonance imaging (MRI), a special imaging test using a magnetic field and radio waves to examine the infected area of skin and soft tissue for patients with cutaneous anthrax.
* All subjects (with or without symptoms) will have the following research procedures:
* a) blood tests to examine immune response to anthrax;
* b) throat swab to test for evidence of anthrax
* c) nasopharyngeal wash to test for anthrax. Water is sprayed into the nostrils and then allowed to drain for collection in a cup;
* d) induced sputum to test for presence of and immune response to anthrax. A mask with a saline mist is placed over the subject s mouth and nose, causing the subject to cough and produce sputum from the lungs. The sputum is collected in a cup this is for individuals 18 and older who do not undergo bronchoscopy, described below.
* Participants 18 years of age and older may have the following optional research procedures:
* a) leukapheresis or plasmapheresis (see description under non-infected, vaccinated individuals above);
* b) lymph node biopsy. A sample of lymph node tissue is surgically removed under local anesthetic;
* c) bronchoalveolar lavage. This 15- to 30-minute procedure is done in the intensive care unit. The mouth, nasal passages, throat and airways are numbed with lidocaine and a thin flexible tube is passed through the nose into the lung airways. Samples of cells and secretions are obtained by rinsing (lavage) the airways with salt water. The fluid is analyzed for infection, inflammatory cells and inflammatory chemicals.

All infected and exposed individuals will have periodic medical history and physical exam evaluations and be offered treatment or prophylaxis (treatment to prevent infection) with antibiotics, according to the guidelines of the Centers for Disease Control and Prevention (CDC). Patients will be monitored for at least 24 months after antibiotic treatment, or longer if circumstances warrant.

Non-infected, vaccinated individuals

1. medical history and physical examination
2. blood tests-- between 10 and 50 ml (2-10 teaspoons) of blood will be drawn at a time, and not more than 450 ml will be taken in a 6-week period. Based on the blood test results, other optional research procedures may be requested
3. leukapheresis to collect white blood cells and plasmapheresis to collect plasma (the liquid part of the blood). For both of these procedures, blood is collected through a needle placed in an arm vein. The blood flows into a special machine that separates it into its components by spinning. The desired components (white cells or plasma) are removed and the rest of the blood is returned to the body through the same needle or a second needle in the other arm.

Detailed Description

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The intentional use of Bacillus anthracis in 2001 as a bioterrorism weapon with fatal consequences renewed interest in past epidemiologic and animal research about pathogenesis and posed new dilemmas about diagnosis and treatment. Cases in the October 2001 US outbreak were theoretically exposed via one dispersal method: aerosolization of Ames strain spores. While some developed the cutaneous anthrax form, others sustained the more serious inhalational disease. Inhaled spores are known to travel to alveolar macrophages and then onto the mediastinal lymph nodes where germination to the bacterium form and toxin release are thought to occur. Infective dose, significance of dormant spores after long-term antibiotic therapy, spectrum of disease and even precise cause of death remain unknown. This observational, prospective natural history study was developed during the 2001 outbreak and is set up to follow participants from the time of exposure through post-recovery (greater than ten years). Healthy vaccinated participants have been included to evaluate serum titers and cell markers in relation to dose and frequency of Anthrax Vaccine Adsorbed (AVA) vaccine.

Conditions

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Anthrax Bacillus Infections

Keywords

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Anthrax Natural History Vaccinated Healthy Volunteer

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Acute Infection (confirmed or suspected)

adults and children with acute anthrax infection

No interventions assigned to this group

AVA Recipient/Healthy Volunteer

healthy adults who have received AVA vaccine

No interventions assigned to this group

Recovered

adults and children in recovering phase of anthrax infection

No interventions assigned to this group

Suspected Exposure

adults and children with suspected exposure to anthrax

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

Subjects at least 3 years old, including pregnant women, are eligible for inclusion if they meet one of the five criteria listed below, are hemodynamically and clinically stable, and agree to stored samples. Women of child-bearing age or potential will not be excluded from participation but pregnancy status will be determined by serum or urine pregnancy test at time of enrollment in order to optimize subsequent evaluation and care.

Although the study is open to participants at least 3 years old, pediatric anthrax cases are historically rare and essentially of the cutaneous type. Therefore, few, if any pediatric subjects are expected.

Decisionally impaired subjects will be included in this study only if a Legally Authorized Representative (LAR) understands and is willing to sign a written informed consent document.

1. Inhalation Anthrax (acute or recovering infection)

CONFIRMED:

--nonspecific febrile illness followed by sepsis and/or respiratory failure

AND

--B anthracis isolation (via culture) from any site OR 2 supportive lab tests

OR SUSPECTED:

--nonspecific febrile illness followed by sepsis and/or respiratory failure with no alternative diagnosis

AND

--one supportive lab test OR direct epidemiological link to a confirmed environmental exposure
2. Cutaneous Anthrax (acute or recovering infection)

CONFIRMED:

--characteristic lesion (papule-\>vesicular-\>depressed black eschar plus or minus edema, erythema, necrosis, or ulceration)

AND

--B anthracis isolation (culture) from any site OR 2 supportive lab tests

SUSPECTED:

--Characteristic lesion with no alternative diagnosis

AND

--one supportive lab test OR direct epidemiological link to a confirmed environmental exposure
3. Gastrointestinal Anthrax (acute or recovering infection)

CONFIRMED:

--Severe abdominal pain often associated with bloody vomiting/diarrhea followed by fever/septicemia

AND

--B anthracis isolation (culture) from any site OR 2 supportive lab tests

SUSPECTED:

--Severe abdominal pain often associated with bloody vomiting/diarrhea followed by fever/septicemia with no alternative diagnosis

AND

--1 supportive lab test OR direct epidemiological link to a confirmed environmental exposure

These definitions were subsequently updated by the CDC in 2010 to accept clinically compatible symptoms plus one of the following: a positive culture, a positive immunohistochemical stain for antigen, a 4-fold increase in anti-PA IgG or a positive documented exposure with detection of DNA via PCR (26).
4. Exposed individuals who are clinically asymptomatic.
5. Past or imminent vaccination in healthy (non-anthrax exposed).
6. Hemodynamically and clinically stable at time of evaluation at NIH.

* Hemodynamically: stable vital signs
* Clinically: no obvious signs of disease progression (e.g. worsening pleural effusions or increasing cutaneous edema)
* acute/newly recovered patients must be receiving standard antimicrobial therapy
7. Participant agrees to stored samples.

Exclusion Criteria

Inability of subject or Legally Authorized Representative (LAR) to understand or subject not willing to sign a written informed consent document.
Minimum Eligible Age

3 Years

Maximum Eligible Age

100 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Mary E Wright, M.D.

Role: PRINCIPAL_INVESTIGATOR

National Institute of Allergy and Infectious Diseases (NIAID)

Locations

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National Institutes of Health Clinical Center

Bethesda, Maryland, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Rosemary McConnell, R.N.

Role: CONTACT

Phone: (301) 761-6645

Email: [email protected]

Mary E Wright, M.D.

Role: CONTACT

Phone: (301) 594-6318

Email: [email protected]

Facility Contacts

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NIH Clinical Center Office of Patient Recruitment (OPR)

Role: primary

References

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Dalton R. Genetic sleuths rush to identify anthrax strains in mail attacks. Nature. 2001 Oct 18;413(6857):657-8. doi: 10.1038/35099687. No abstract available.

Reference Type BACKGROUND
PMID: 11606978 (View on PubMed)

Shafazand S, Doyle R, Ruoss S, Weinacker A, Raffin TA. Inhalational anthrax: epidemiology, diagnosis, and management. Chest. 1999 Nov;116(5):1369-76. doi: 10.1378/chest.116.5.1369.

Reference Type BACKGROUND
PMID: 10559102 (View on PubMed)

Centers for Disease Control and Prevention (CDC). Update: Investigation of bioterrorism-related anthrax and adverse events from antimicrobial prophylaxis. MMWR Morb Mortal Wkly Rep. 2001 Nov 9;50(44):973-6.

Reference Type BACKGROUND
PMID: 11724150 (View on PubMed)

Related Links

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Other Identifiers

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020110

Identifier Type: -

Identifier Source: org_study_id

02-I-0110

Identifier Type: -

Identifier Source: secondary_id